富亮氨酸胶质瘤失活1蛋白抗体阳性边缘叶脑炎四例

目的总结富亮氨酸胶质瘤失活1(LGI1)蛋白抗体阳性边缘叶脑炎(LE)的临床特征以利于早期诊断及治疗。方法对4例LGI1-LE的临床、实验室、脑电图及影像学资料进行分析,并对其进行2~8(平均5.5±2.5)个月的随访。结果该组患者均以癫痫发作起病,表现为面臂肌张力障碍(FBDS)、部分性发作、全面强直阵挛发作。1例(例3)出现轻度认知功能障碍。发作间期EEG显示为正常、额颞区为著慢波或尖波;发作期EEG均未发现发作起源。MRI检查1例(例3)右侧颞叶内侧T2加权相高信号。所有患者血清LGI1抗体阳性,3例患者脑脊液LGI1抗体阳性。2例患者轻度低钠血症。1例(例2)患者诊断小细胞肺癌。抗癫痫药物对发作控制不佳。免疫治疗除例2外均有效。结论 LGI1-LE整体预后较好。识别特征性FBDS,尽早开始免疫治疗可以改善患者预后。     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘叶脑炎的临床特点并文献复习

目的 探讨富亮氨酸胶质瘤失活1蛋白(LGI1)抗体阳性边缘叶脑炎的临床特点。方法 对本院收治的1例LGI1抗体阳性的边缘叶脑炎患者的诊治过程进行回顾性分析并复习相关文献。结果 患者为青年女性,亚急性起病,临床主要表现为记忆力下降、癫痫、闭经、情绪障碍。血和脑脊液LGI1抗体阳性; MRI检查T₂及Flair序列可见双侧颞叶内侧、海马高信号病灶; PET-CT示双侧颞叶内侧、海马代谢活性对称性降低。经激素和免疫球蛋白联合治疗,疗效显著。结论 LGI1抗体阳性边缘叶脑炎以记忆力下降、癫痫发作为主要临床表现; 病灶主要累及双侧颞叶内侧、海马; 具有较好的免疫治疗效果,及时的诊断及治疗有助于患者的恢复。     

富亮氨酸胶质瘤失活1蛋白抗体相关脑炎研究进展

富亮氨酸胶质瘤失活1蛋白抗体相关脑炎( leucine-rich glioma-inactivated 1,LGI1)约占边缘性脑炎的30％,是最常见的边缘性脑炎,也是继抗NMDAR脑炎之后第二常见的自身免疫性脑炎.其临床特点包括癫痫发作、记忆力下降、低钠血症等.LGI1抗体相关脑炎如果及时进行免疫调节等治疗,可预后良...     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘系统脑炎7例临床分析

目的总结富亮氨酸胶质瘤失活1蛋白(LGI1)抗体阳性边缘系统脑炎临床特点及免疫治疗反应,以提高对该病的认识。方法分析2012-03-2014-07在天坛医院神经内科就诊的7例LGI1抗体阳性边缘系统脑炎患者的临床、实验室检查资料,总结不同治疗方案患者的预后。结果 7例患者以精神行为异常、认知功能下降、颞叶癫痫为主要临床表现。均行脑脊液检查,其中4例常规、生化正常,3例表现为蛋白轻度升高。3例患者出现顽固性低钠血症。所有患者肿瘤标志物、影像学筛查均未发现肿瘤,副肿瘤抗体(抗-Hu、-Yo、-Ri、-Ma2)阴性。4例脑电图检查异常,表现为局灶性癫痫样放电或节律减慢。4例MRI检查Flair及T2序列可见颞叶内侧高信号病灶。7例患者经免疫调节治疗预后良好。结论 LGI1抗体阳性边缘系统脑炎以认知功能下降、癫痫发作为主要临床表现,常伴有低钠血症,极少伴有肿瘤;病灶累及颞叶内侧为主,T2或Flair序列为高信号;具有较好的免疫治疗效果,及时的诊断及治疗有助于患者的恢复。     

富亮氨酸胶质瘤失活1蛋白抗体阳性相关免疫脑炎1例临床分析并文献复习

目的 报道富亮氨酸胶质瘤失活1蛋白(LGI1)自身抗体阳性免疫脑炎1例,结合文献分析,以提高临床医师对该病的认识。方法 结合文献分析该LGI1抗体阳性相关免疫脑炎患者的临床资料,并分析疗效。结果 中年男性急性起病,以肢体麻木、意识丧失、精神症状、癫痫间发作、四肢不自主运动为主要临床表现并伴低钠血症。脑脊液细胞、生化、免疫均正常,肿瘤相关抗原未见异常,副肿瘤抗体阴性,影像学检查排除颅内肿瘤。脑电图检查示右侧额颞导多量阵发性慢波异常及棘慢综合波。双侧海马区冠状位FLAIR序列提示双侧高信号,血清及脑脊液LGI-1抗体均(++)。结论 LGI1自身抗体阳性免疫脑炎以颞叶癫痫间作、精神异常为主要临床表现,常伴有低钠血症,病灶累及颞叶内侧为主,海马冠状位FLAIR序列常为高信号,免疫调节治疗及大剂量激素效果显著。     

复发性抗富亮氨酸胶质瘤失活1蛋白脑炎临床分析

目的分析复发性抗富亮氨酸胶质瘤失活1蛋白(LGI1)脑炎的临床特点、诊断、治疗及预后情况。方法收集郑州大学第一附属医院2015-01—2019-01确诊抗LGI1脑炎患者,回顾性分析复发患者临床表现、实验室及影像检查、治疗及预后。结果 37例抗LGI1脑炎确诊患者中,13例复发,6例有多次复发。4例复发期出现新的症状,9例复发症状为首次发病症状的再次出现。认知功能下降、癫痫、精神症状及自主神经症状为复发患者首次发病和复发常见症状。13例复发患者有10例接受序惯口服激素治疗,第1次复发前口服激素平均时间为2.25个月。13例患者死亡6例。10例患者首次复发重启免疫治疗。预后良好(mRS≤2分)患者复发至重启免疫治疗平均时间2.6 d,预后差患者33.5 d。结论抗LGI1脑炎复发比较常见,患者复发症状多为首次发病症状的再次出现。及时重启免疫治疗的复发患者,预后良好。     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘系统脑炎一例临床特点

目的 探讨富亮氨酸胶质瘤失活1蛋白(LGi1)抗体阳性边缘系统脑炎临床特点、诊断及免疫治疗反应,以期引起临床重视.方法 报道国内首例LGi1抗体阳性边缘系统脑炎患者的诊治经过,结合临床表现、结构及功能影像学、脑电图、免疫治疗反应以及相关文献,分析该疾病的特点.结果 患者为老年男性,表现为亚急性起病的近期记忆功能减退,抗癫痫药物抵抗的频繁、短暂的面-臂肌张力障碍发作,顽固性低钠血症,影像学提示颞叶内侧区受累.血和脑脊液LGi1抗体阳性.经静脉丙种球蛋白治疗,临床痊愈.结论 LGi1抗体阳性边缘系统脑炎有独特的临床表现和较好的免疫治疗效果,及早诊治可明显改善预后.     

抗富亮氨酸胶质瘤失活1蛋白和抗髓鞘少突胶质细胞糖蛋白双抗体阳性的边缘叶脑炎1例

介绍1例抗富亮氨酸胶质瘤失活1蛋白(LGI1)和抗髓鞘少突胶质细胞糖蛋白(MOG)双抗体阳性的边缘叶脑炎患者。患者为中年男性, 既往有视网膜静脉阻塞病史, 本次发病主要症状为颞叶癫痫、面臂肌张力障碍、自主神经功能障碍等;头颅磁共振成像示右侧海马长T2信号、无强化、灌注正常;脑电图示发作间期阵发性慢波、尖慢波;血抗MOG抗体、血和脑脊液抗LGI1抗体双阳性, 主要诊断为边缘叶脑炎, 给予激素和丙种球蛋白治疗后症状好转, 复查双抗体均转阴。该抗LGI1/MOG双阳性病例较罕见, 且临床症状和影像学表现并非与单一抗体阳性患者完全一致, 有其不同特点。文中对该病例临床资料进行报道以期进一步加深临床医师对该病的认识。     

富亮氨酸胶质瘤失活基因在胶质瘤中的表达

目的 探讨胶质瘤组织富亮氨酸胶质瘤失活基因1(LGI1)mRNA的表达及与细胞增殖活性之间的关系.方法 采用逆转录聚合酶链反应(RT-PCR)法对30例脑胶质瘤组织、2例脑膜瘤、2例瘤旁及2例颅脑损伤内减压脑组织标本进行半定量检测,同时采用S-P免疫组化法检测Ki-67标记指数.结果 脑胶质瘤组的LGI1 mRNA表达水平低于正常脑组织和脑膜瘤(P＜0.05).脑胶质瘤中,WHO Ⅳ级的胶质瘤LGll mRNA表达低于WHOⅡ级和Ⅲ级胶质瘤(P＜0.05),与Ki-67标记指数呈负相关关系(r=-0.621,P＜0.01).结论 LGI1基因的表达与Ki-67标记指数呈负相关,提示LGI1与胶质瘤的发生关系密切.     

抗LGI1抗体相关脑炎患者的临床、脑电图及影像学特点

目的 探讨抗富亮氨酸胶质瘤失活蛋白1(LGI1)抗体相关脑炎患者的临床、脑电图及影像学特点,为临床诊断治疗提供参考。方法 选取2020年6月至2022年4月江苏省苏北人民医院神经内科收治的10例抗LGI1抗体相关脑炎患者,总结其临床表现、脑电图、影像学特点、治疗及预后。结果 10例抗LGI1抗体相关脑炎患者表现为近记忆障碍4例、精神行为异常2例、面-臂肌张力障碍(FBDS)3例、全面性强直阵挛发作4例,局灶性发作5例。脑电图异常6例,主要为癫痫样放电、弥漫性及阵发性慢波。头颅MRI异常4例,主要累及海马、颞叶或基底节区。头颅动脉自旋标记(ASL)异常6例,主要为海马、颞叶或全脑灌注增高。所有患者均接受免疫治疗,其中9例行抗癫痫发作治疗。除1例患者拒绝后续治疗后死亡,9例预后良好。结论 抗LGI1抗体相关脑炎的临床表现为癫痫发作、FBDS、近记忆障碍、精神行为异常及低钠血症等,可伴甲状腺功能抗体升高,很少合并肿瘤,易出现颞叶及海马等局灶性影像学以及脑电图异常,免疫治疗疗效较好。     

Three cases of antibody-LGI1 limbic encephalitis and review of literature

Purpose: Antibody-LGI1 limbic encephalitis (LGI1-Ab LE) is an anti-neuronal surface antigen-related autoimmune encephalitis. we report three cases of LGI1-Ab LE, describe the characteristics of clinical manifestation, course of evolution, imaging manifestation and treatment outcomes.

Methods: Data from patients diagnosed with LGI1-Ab LE in the Second Hospital, Hebei Medical University, from June 2016 to July 2017, were retrospectively collected and analyzed. We followed up the patients for 90 days.

Results: Two of the three patients were females, the average age of onset is 53 years old. Epilepsy is the most common clinical manifestations, and one of patients developed faciobrachial dystonic seizures (FBDS), which was recently described as a characteristic feature of LGI1-Ab LE. All patients had cognitive impairment in different degrees and abnormal signal of hippocampus in cranial MRI. All serum LGI1 antibodies were positive, whereas one LGI1 antibodies of CSF were negative. All patients accepted first-line immune therapy and had a good outcome.

Conclusion: LGI1-Ab LE, which is an autoimmune disease, is rare clinically and mostly nonparaneoplastic. We suggest that LGI1-Ab LE be considered in any patient with acute or subacute onset, cognitive dysfunction , various types of seizures, accompanied by mental disorders and hyponatremia, MR showed the involvement of the limbic system. It is necessary to have LE-related antibodies tested. Early immunotherapy can significantly improve the patient's overall prognosis. At the same time, we should also pay attention to the possibility of potential tumors.     

LGI‐1 antibody encephalitis in a seven‐year‐old girl

LGI‐1 antibody encephalitis is a rare autoimmune limbic encephalitis which has been reported predominantly in adults. Seizures in LGI‐1 antibody encephalitis exhibit significant semiological variability. Faciobrachial dystonic seizures are characteristically seen in this condition and have so far been described only in adults. Other seizure types have also been reported. We describe the case of a seven‐year‐old girl with LGI‐1 limbic encephalitis who presented with acute new‐onset seizures, and rapidly deteriorated over the course of a few weeks with very frequent seizures and encephalopathy, becoming non‐verbal and non‐ambulatory. The electroclinical presentation of this child with LGI‐1 encephalitis makes this case unique and further highlights the importance of a high index of suspicion for diagnosis in young children. Early diagnosis can lead to prompt and appropriate treatment with immunotherapy, and potential harmful treatments such as pharmacological coma can be avoided. To the best of our knowledge, this is the youngest case ever reporter. [Published with video sequences]     

A case of pediatric anti-leucine-rich glioma inactivated 1 encephalitis with faciobrachial dystonic seizure

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of autoimmune encephalitis. A characteristic faciobrachial dystonic seizure (FBDS) is also frequently associated with this disease. Although primarily reported in the adult population, reports of its occurrence in the pediatric population are rare. Here, we describe a case of a 6-year-old girl diagnosed with anti-LGI1 encephalitis that presented with cognitive decline and FBDS.Case presentationThe girl was referred to a pediatric neurology department for uncontrolled seizures and dyskinesia. She initially presented with a memory deficit, abnormal movement of the limbs and trunk, and ataxia. Her cerebrospinal fluid exam was unremarkable, but her brain MRI showed focal T2 high signal intensity in the left anterior putamen and right caudate nucleus. In addition, there were refractory episodes of brief tonic or dystonic movement of the face and arms that were suggestive of FBDS. She was initially treated with intravenous methylprednisolone and phenobarbital, then given another pulse of methylprednisolone and intravenous immunoglobulin as her symptoms persisted. Tests for neuronal autoantibodies revealed the presence of anti-LGI1 antibodies. Subsequent human leukocyte antigen (HLA) typing resulted in the identification of HLA-DRB1 DR7(*07:01 g) DR9(*09:01 g). Screening for thymoma and other neoplasms showed no signs of a tumor. She was treated with rituximab, tocilizumab, and antiseizure medications, including oxcarbazepine, valproic acid, and lamotrigine. Her FBDS and cognitive symptoms showed substantial improvements.ConclusionWhile it is known that anti-LGI1 encephalitis responds well to immunotherapy, our patient showed an incomplete response, requiring further therapy. This is the first report of a pediatric patient with anti-LGI1 encephalitis treated with tocilizumab.     

Frontal infraslow activity marks the motor spasms of anti-LGI1 encephalitis

Objective

The clinical and electrographic features of seizures in anti-LGI1 encephalitis are distinct from those seen in other autoimmune encephalitides or non-encephalitic epilepsies. One electroclinical phenomenon specific to the condition consists of lateralized motor spasms, known as faciobrachial dystonic seizures (FBDS). An electrodecremental pattern overriding a “DC shift” has been described as the EEG correlate of these spasms. We sought to further characterize this pre-spasm infraslow activity (ISA).

Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission

Purpose: Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well‐recognized form of LE is associated with voltage‐gated potassium channel complex antibodies (VGKC‐Abs) in the patients’ sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC‐Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy‐fiber (MF)‐CA3 pyramidal cell synapses. Methods: We compared the effects of LE and healthy control IgG by whole‐cell patch‐clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. Results: We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF‐evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF‐CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α‐dendrotoxin (120 nm ), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG‐mediated effects. Conclusions: This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability.     

A 9-year neuropsychological report of a patient with LGI1-associated limbic encephalitis

Introduction: Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is an autoimmune disorder associated with antibodies to voltage-gated potassium channels (VGKC). It is a non-paraneoplastic and partially reversible encephalitis that can be diagnosed via serological testing. Untreated LGI1-LE can be associated with neurocognitive as well as neuropsychiatric sequelae. Here we report the neuropsychological and clinical profile of a patient with LGI1-LE following three different treatment approaches: plasmapheresis (PA), intravenous immunoglobulin (IVIG), and corticosteroids (CO).

Method: We investigated our patient with 10 neuropsychological evaluations obtained over a 9-year follow-up period. Multiple MRI scans, EEG recordings, neurological examinations, and serum tests were also obtained.

Results: The neurocognitive profile of our patient was characterized by long-term memory impairment (verbal and visual-spatial), and deficits in aspects of executive functioning and language. Neuropsychiatric symptoms of depression and anxiety were noted intermittently.

Conclusions: Non-specific treatment prior to diagnosis had marginal effects on neurocognitive profile, neuropsychiatric symptoms, or control of epileptic seizure. In contrast, specific treatments for LGI1-LE following diagnosis resulted in neurocognitive improvement and epileptic control. Among the three treatments, IVIG and CO had the most beneficial impact on neurocognitive status, likely due to the continuity of administration.     

A case of bilateral limbic and recurrent unilateral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein antibody positivity

BackgroundAnti-myelin oligodendrocyte glycoprotein (MOG) antibody can be detected not only in acute disseminated encephalomyelitis or optic neuritis but also in limbic or cortical encephalitis. However, no previous reports have demonstrated a relapsing case of these two types of encephalitis.Case reportAn 11-year-old girl presented with fever, headache, abnormal behavior, focal impaired awareness seizures (FIAS) on the left side, and MRI hyperintensities in the bilateral amygdala, hippocampus, and right posterior temporal cortex. The symptoms were alleviated with two courses of intravenous methylprednisolone (IVMP) and one course of immunoglobulin. At 16 years of age, the patient returned with left-sided headache and MRI hyperintensities in the left temporal, parietal, and insular cortices, which improved after 3 courses of IVMP. Oral prednisolone (PSL) was tapered over 6 months, when FIAS reappeared on the right side of the body. MRI showed recurrence in the same regions as in the second episode. She received 3 courses of IVMP, followed by gradually tapered PSL without relapse for 1.5 year. Anti-MOG antibodies were positive in both serum and the cerebrospinal fluid prior to treatment in all three episodes.ConclusionOur results revealed that anti-MOG antibody-related bilateral limbic and unilateral cortical encephalitis can manifest with a variety of phenotypes over time in the same patient.